Sorafenib Tosylate in Treating Patients with Advanced Liver Cancer and Hepatitis C Infection

Inclusion Criteria

• Participants must have histologically or/and radiologically confirmed advanced hepatocellular carcinoma (HCC); radiographic diagnosis needs typical findings of HCC by radiographic method i.e. on multi-dimensional dynamic computed tomography (CT), CT hepatic arteriography (CTHA)/CT arterial portography (CTAP) or magnetic resonance imaging (MRI)
• Detectable HCV RNA with anti-HCV-positivity
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelets >= 50,000/mm^3
• Hemoglobin >= 8 g/dl
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 6 x upper limits of normal
• Total bilirubin =< 3.0 mg/dL
• Renal function creatinine =< 2.0 mg/dL and/or creatinine clearance >= 50 ml/min
• Child-Pugh score =< 7 (Child A-B)
• Barcelona Clinical Liver Cancer Classification (BCLC) B or C
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Life expectancy of greater than 3 months
• Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure
• Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
• Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at the signing of the informed consent form (ICF) until at least 30 days after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator or a designated associate
• Subject must be able to swallow and retain oral medication

Exclusion Criteria

• Patients with undetectable HCV RNA
• Patients who are not able to sign inform consent
• Uncontrolled hypertension (systolic pressure > 140 mmHg or diastolic pressure > 90 mmHg (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE] version [v]4.0) on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including: * Congestive heart failure – New York Heart Association (NYHA) > class II * Active coronary artery disease * Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin * Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before study entry
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) within 6 months of informed consent
• Subject with any pulmonary hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 2 or higher within 4 weeks before randomization; any other hemorrhage/bleeding event of NCI-CTCAE v4.0 grade 3 or higher within 4 weeks before study entry
• Subjects who have used strong cytochrome P450, family 3, subfamily A, polypeptide A (CYP3A4) inducers (eg, phenytoin, carbamazepine, phenobarbital, St. John’s wort [Hypericum perforatum], dexamethasone at a dose of greater than 16 mg daily, or rifampin [rifampicin], and/or rifabutin) within 28 days before study entry
• Subjects with any previously untreated or concurrent cancer that is distinct in primary site or histology from breast cancer except cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before randomization are allowed; all cancer treatments must be completed at least 3 years prior to study entry (i.e., signature date of the informed consent form)
• Presence of a non-healing wound, non-healing ulcer, or bone fracture
• History of organ allograft (including corneal transplant)
• Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
• Any malabsorption condition
• Women who are pregnant or breast-feeding
• Inability to comply with the protocol and/or not willing or not available for follow-up assessments
• Major surgery within 30 days prior to start of study drug
• Any condition which, in the investigator’s opinion, makes the subject unsuitable for trial participation
• EXCLUDED THERAPIES AND MEDICATIONS, PREVIOUS AND CONCOMITANT
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than sorafenib
• Prior use of sorafenib
• Concurrent use of another investigational drug or device therapy (i.e., outside of study treatment) during, or within 4 weeks of trial entry (signing of the informed consent form)
• Patients treated with interferon or other anti-HCV therapy within 3 months prior to study entry
• Previous assignment to treatment during this study